Purpurin specifically inhibits Candida albicans efflux pump Cdr2p

Document Type

Conference Proceeding

Publication Date

2013

Abstract

Background and aim: A major drug resistance mechanism of the Candida fungi is mediated by membrane-bound efflux pumps. Compounds that inhibit efflux pump activity may have therapeutic relevance. Our earlier studies demonstrated the novel antifungal activity of purpurin against Candida species in vitro; and the inhibitory effect on energy-dependent efflux pumps. The aim of the present study was to examine the differential effect of purpurin on C. albicans efflux pumps Cdr1p and Cdr2p. Materials & methods: Engineered Saccharomyces cerevisiae strains that heterologously overexpressed C. albicans Cdr1p and Cdr2p were used (provided by Prof. Richard Cannon of the University of Otago). The MIC of purpurin and fluconazole (FLC) against the S. cerevisiae strains were determined by a modified microdilution method; and defined as the lowest concentration leading to 80% inhibition of visible growth compared with the solvent control (1% DMSO). Chemosensitization of the S. cerevisiae strains to FLC by purpurin were assessed by a chequerboard microdilution assay. The fractional inhibitory concentration index (FICI) was defined as the sum of the MIC of each compound when used in combination divided by the MIC of the compound alone. The interactions were categorized as either synergistic (FICI ≤ 0.5), indifferent (0.5 < FICI ≤ 4) or antagonistic (FICI > 4). Results: Purpurin chemosensitized C. albicans Cdr2p to FLC (FICI = 0.375); whereas the interaction between purpurin and FLC on C. albicans Cdr1p was “indifferent”. Conclusion: Purpurin is a C. albicans Cdr2p-specific inhibitor.

Source Publication

The 5th Congress of European Microbiologists (FEMS 2013), 2013 Jul 21-25, Liepzig, Germany

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